The involvement of TNFRSF25 in age-related hearing loss

Hearing loss is a prevalent sensory condition that affects the ability to perceive sounds. Hair cells play a vital role in hearing by converting mechanical sound vibrations into electrical signals that are transmitted to the brain. In humans, if damaged, these specialized sensory cells do not regenerate, leading to reduced sensitivity to sound, difficulty understanding speech, and deafness. The incidence of hearing loss increases with age, but it can also occur earlier due to genetic predisposition or environmental factors such as exposure to noise or ototoxic medications. Epigenetic mechanisms play a significant role in age-related hearing loss (ARHL) by regulating gene expression without changing the underlying DNA sequence. Aberrant DNA methylation patterns have been linked to ARHL. In this study, by performing an epigenome-wide association study in a cohort of 30 ARHL patients, we found a correlation between a specific CpG site methylation level proximal to the TNFRSF25 gene, with an impaired hearing threshold. Interestingly, Tnfrsf25 absence in mice cause ARHL, severe hair cell depletion, and degeneration of nerve fibers. Taking together these results suggests a crucial role of Tnfrsf25 expression in hearing maintenance.